During aging, the female rat demonstrates a sequential change in reproductive function as revealed by its progression from the regular to irregular cyclicity to a complete cessation of ovulatory cycles. These events occur long before the functional follicles are depleted from the ovaries, and there is a prolonged phase of post-reproductive life. We propose varied experimental approach to study the functional capacity of aging rat ovaries, pituitary and hypothalamus during this reproductive aging transition. During each phase of this transition, experiments will be undertaken to determine the daily 24-hr patterns of ovarian steroid and pituitary gonadotropin and prolactin levels in the circulation (by radioimmunoassays), and to correlate these with the concurrent changes in gonadotropin binding activity in the ovaries and in steroid receptor levels in the hypothalamus and anterior pituitary (by receptor assays). Specifically, the temporal relationship between the circulating levels of ovarian steroids and pituitary gonadotropins will be analyzed to determine the effects of estradiol and progesterone on a possible decrease in FSH secretion. In the rats, hormone concentrations within the follicular fluid of developing follicles also will be measured and correlated with the ovarian activity. Both in vivo and in vitro studies will be performed to determine the capacity of aging rat ovaries to produce steroids in response to gonadotropin stimulation. These in vitro studies may be best performed by a co-incubation system with the ovarian tissue and the serum obtained from the rat. With chronic cannula, longitudinal studies will be performed on the same rat during different phases of aging for studying any chronological changes in circulating hormone patterns, in ovarian responsiveness and in ovarian steroid feedback effect on pituitary gonadotropin secretion with advancing age. To test our working hypothesis that a possible decrease in pituitary FSH secretion is the key determinant in the initiation of irregular ovulatory function during aging, experiments will be undertaken to determine whether approppriate FSH administration can revert the estrous cycles from irregular to regular patterns and to restore regular ovulatory function.